Lee S G, Yoon S J, Kim C D, Kim K, Lim D S, Yeom Y I, Sung M W, Heo D S, Kim N K
Cancer Research Center, Department of Internal Medicine, College of Medicine, Seoul National University, Korea.
Cancer Gene Ther. 2000 Oct;7(10):1329-35. doi: 10.1038/sj.cgt.7700237.
Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.
尽管腺病毒在体外具有高转染效率已有充分记录，但在实体瘤模型中腺病毒载体在体内是否有效仍不清楚。在我们的初步实验中，在瘤内注射腺病毒载体后，肿瘤组织的转导仅限于注射部位周围。为了提高体内转导效率，我们在动物模型中尝试了腺病毒载体与脂质体的联合使用。携带人胎盘碱性磷酸酶的腺病毒（AdALP）和脂质体转染试剂或1,3 - 二油酰氧基 - 2 -（6 - 羧基精胺基）丙酰胺分别用作标记基因和阳离子脂质体。与单独使用腺病毒相比，携带小鼠粒细胞 - 巨噬细胞集落刺激因子的AdALP腺病毒（AdmGM - CSF）与脂质体联合使用时，CT26肿瘤细胞系中的转染效率提高了15倍以上，表明联合治疗的可行性。在动物模型中，脂质体与AdALP联合使用时，标记基因在肿瘤块中的分布更深更广。我们得出结论，使用阳离子脂质体可以克服腺病毒载体在实体瘤模型中直接应用的局限性。这种方法将有助于在临床试验中更有效地递送腺病毒载体。
